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Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo

This study investigated evaluation of the DNA damage in tumour cells, as well as irreversible cell damage leading to apoptosis induced in vivo by the combined application of cisplatin and inhalation anaesthetics, such as sevoflurane, halothane or isoflurane. Genotoxicity of these anaesthetics on Ehrlich ascites tumour cells of mice, alone, or in combined application with cisplatin, was estimated by using the alkaline Comet assay. The percentage of EAT cells apoptosis was quantified by flow cytometer. Groups of EAT bearing mice were (i) treated intraperitoneally with cisplatin, (ii) exposed to repeated anaesthesia with inhalation anaesthetic, and (iii) were subjected to a combined treatment of exposure to inhalation anaesthetic after receiving cisplatin for three consecutive days. Sevoflurane, halothane and isoflurane caused strong genotoxic effect on tumour cells in vivo, halothane presenting the strongest and sevoflurane weakest effect. Unexpectedly, repeated anaesthesia with halothane caused more severe DNA damage compared to cisplatin treatment alone, whereas the combined treatment with cisplatin and halothane did not result in synergistically increased genotoxicity. Tested anaesthetics alone showed no direct effect on programmed cell death, although sevoflurane and especially halothane decreased the number of living EAT cells in peritoneal cavity lavage. Repeated anaesthesia with isoflurane had a stimulatory effect on EAT cells proliferation and inhibited tumour cells apoptosis (6.11%), related to control group (10.26%). As expected, cisplatin caused massive apoptosis of EAT cells (41.14%) and decreased the number of EAT living cells in peritoneal cavity. Combined cisplatin and isoflurane treatment additionally increased the percentage of EAT cells apoptosis to 51.32%. Combined treatment of mice with cisplatin and all three mentioned anaesthetics increased a number of living tumour cells in peritoneal cavity compared to cisplatin treatment of mice alone. These results suggest that inhalation anaesthetics may protect tumour cells from genotoxic and cytotoxic effect induced by cisplatin.

genotoxicity; cytotoxicity; cisplatin; inhalation anaesthetics; Ehrlich ascites tumour; mice

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